Non-vectorial Integration of Intersectional Short-Pulse Stimulation Enables Enhanced Deep Brain Modulation and Effective Seizure Control

Transcranial electrical stimulation (TES) holds promise to treat neurological disorders, but its efficacy is limited by poor spatial focality and depth of penetration. Here, we examined the potential utility of Intersectional Short-Pulse (ISP) stimulation of deeper brain penetration. Using computational modeling and in vivo patch-clamp recordings in rats, we demonstrate that neurons integrate ISP-induced electric fields in a non-vectorial manner. This mechanism allows ISP to overcome some limits of conventional TES, achieving spatially limited stimulation across cortical and subcortical structures. In a rat model of temporal lobe epilepsy, closed-loop ISP stimulation significantly outperformed conventional TES in reducing seizure duration and severity. ISP reduced hippocampal seizure duration by 49% and 41% compared to sham stimulation and conventional TES and significantly reduced motor seizure severity. Our findings demonstrate that ISP stimulation can rapidly terminate hippocampal seizures, offering a potential new approach for non-invasive neuromodulation with applications across diverse neurologic and psychiatric disorders.